The European Union Clinical Trial Regulation No. 536/2014, which went into effect on January 31, 2022, has introduced the most significant changes to the processes for clinical trial applications in at least the past 15 years. The new regulation will undoubtedly address longstanding challenges around transparency and multi-country submissions and will contribute to more innovation. However, the amount of change a regulation of this magnitude drives can also be the source of tremendous stress on organizations, as the entire life sciences ecosystem adapts to new tools and processes.

The European Medicines Agency (EMA) has a stated goal in EU 536/2014 to foster innovation through a simpler clinical trial application process across Member States while increasing transparency of clinical trials and their results. It included the development of a new EU Portal and EU Database, collectively named the Clinical Trial Information System (CTIS), where clinical trial information is submitted for agency and public consumption. The source of data entered into the CTIS will frequently include content from electronic Trial Master File (eTMF) systems.

To achieve compliance, the regulation states:

“A clinical trial master file (TMF), containing relevant documentation to allow effective supervision (monitoring by the sponsor and inspection by Member States), should be kept by the sponsor and by the investigator. The clinical trial master file should be archived appropriately to allow for supervision after the clinical trial has ended.”

As EMA’s new regulation takes effect, let’s consider three key functions that your eTMF must have to achieve compliance and maintain organizational success.

1. Verification of clinical TMF health

Article 57 states that the clinical eTMF must be up-to-date and contain all essential documents that enable an auditor or monitor to verify sound trial conduct with data of high quality.  This data must be readily available and directly accessible to Member States.

Your eTMF must have robust tools to enable timely and high-quality collection and tracking of critical documentation. In addition, dashboards should give sponsors, investigators, and auditors the ability to quickly assess the TMF health based on completeness, timeliness, and quality. The dashboards should also have drill-down capabilities so the supporting details for these metrics are readily available.

2. Archiving of the clinical TMF

Per Article 58 of the regulation, the sponsor and the investigator must archive the content of the clinical trial master file for at least 25 years after the end of the clinical trial in a way that ensures it is readily available and accessible upon request to the competent authorities.

As the number of historical plus active clinical trials grows within an organization, so does the cost of maintaining an accessible TMF across a 25-year horizon. Thus, clinical trial sponsors and investigators need solutions that enable a completed study to be moved from an eTMF with full functionality (upload, workflows, etc.) to a lower cost alternative that enables easy read-only access to completed studies.

While lowering costs during the archive period is important, the clinical trial sponsor cannot risk security breaches that have the potential to expose patient data or other sensitive information. Access to electronic TMFs need to be tested on a regular basis, and support to regulatory inspectors must be available on short notice to ensure their duties can be performed without delay.

3. Management of multiple copies – redacted and non-redacted

A key aspect of the new regulation is the publishing of all clinical trial data submitted to the EMA to enable re-analysis by researchers. However, there are exceptions to conceal personal data and commercially confidential information, and redacted versions of documents are expected. Redacted versions will be published to the public after the trial ends. That said, both redacted and unredacted copies of documents need to be submitted to the EMA. Details are described in an appendix on disclosure rules.

To meet these requirements, a sponsor’s electronic TMF must be able to intelligently manage both redacted and unredacted document copies and recognize the relationships between the two.

The future of eTMF is agile

IQVIA Technologies’ Digital Site Suite includes an array of products that support site-sponsor-CRO interactions and document flow. IQVIA eTMF, formerly known as Wingspan, is an agile, cloud-based application, geared toward supporting organizations and adapting their TMF for regulatory changes.

• Instant insights into TMF health – Via a highly intuitive interface, the IQVIA eTMF provides configurable dashboards and analytics tools for planning and tracking, providing instant awareness of TMF health. Available immediately upon log-in, users can understand and correct quality, completeness, and timeliness issues proactively for nonstop audit-readiness.

• eArchive – Sponsors are able to move completed studies from a full-functioned eTMF to IQVIA eArchive, which has the same user-friendly interface as IQVIA eTMF to enable the quick and readily available read-only access needed for inspections and audits. Since many of the full-functioned eTMFs are not applicable for these closed studies, eArchive provides a low-cost solution for long-term archival. Documents are protected by state-of-the-art security in our data centers, which are certified for Management & Operations (M&O) Excellence by the Uptime Institute and annually certified for Statements on Standards for Attestation Engagements (SSAE) 16 Type II by the American Institute of CPAs (AICPA) and for the International Organization for Standardization (ISO) 27001 on security techniques for information technology.

• Copy Management – The IQVIA eTMF 3.0 includes support for identifying and maintaining redacted content available in the system. Based on how the document type is defined, a document can be marked as containing redacted content during indexing. If a document is marked as containing redacted content, the system will remind the user to create a relationship to the corresponding “unredacted” document placeholder. Additional filtering for display or export of only redacted documents is supported.

Regulations are changing globally at a pace faster than we have ever seen before. Adopting an eTMF solution that is agile and adaptable will not only help your organization consistently maintain compliance but also help keep researchers on the cutting edge of medical innovation.

If you would like to discuss the new EMA regulations with the IQVIA eTMF product or support team, please send me an email. For more information about our product, visit www.iqvia.com/eTMF.

IQVIA Technologies has assessed the impact of new European Clinical Trial Regulations on TMF content and process with business and technology leaders across our organization. IQVIA is an active supporter of the TMF Reference Model group, which hosted an online workshop on 07-Apr-2022 covering this important topic. A recording of the workshop is available on www.tmfrefmodel.com.

IQVIA will continue to stay in front of emerging guidance and regulations from EMA, FDA and other regulatory bodies in the life sciences industry. We also look forward to continuing our collaboration with industry leaders through the IQVIA eTMF User Group, which meets formally and informally throughout the year.